Clinical remission of Merkel cell carcinoma after treatment with imatinib

Loader, Dagmara Ewa; Feldmann, Robert; Baumgartner, Magdalena; Breier, Friedrich; Schrama, David; Becker, Jürgen C.; Steiner, Andreas

doi:10.1016/j.jaad.2013.03.042

Cited by 31 publications

(18 citation statements)

References 3 publications

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“…Interestingly, PDGFRa was found frequently mutated in other types of tumours including GISTs [34] where the presence of the specific mutation (D842V) is used to predict response to Imatinib Mesylate [35]. This ''GIST'' activating mutation [24] was detected in 2 MCC cases.…”

Section: Discussionmentioning

confidence: 99%

Correlation of Merkel cell polyomavirus positivity with PDGFRα mutations and survivin expression in Merkel cell carcinoma

Batinica

Akgül

Silling

et al. 2015

Journal of Dermatological Science

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Section: Discussionmentioning

confidence: 99%

Correlation of Merkel cell polyomavirus positivity with PDGFRα mutations and survivin expression in Merkel cell carcinoma

Batinica

Akgül

Silling

et al. 2015

Journal of Dermatological Science

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“…It appears that although MCC may express c-kit, activating mutations in the gene are generally absent. However, there is one case report of clinical remission with imatinib in a patient with MCV-positive MCC [83]. …”

Section: Emerging Treatmentsmentioning

confidence: 99%

Merkel Cell Carcinoma Therapeutic Update

Cassler

Merrill

Bichakjian

et al. 2016

Curr. Treat. Options in Oncol.

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Opinion statement Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Early-stage disease can be cured with surgical resection and radiotherapy (RT). Sentinel lymph node biopsy (SLNB) is an important staging tool, as a microscopic MCC is frequently identified. Adjuvant RT to the primary excision site and regional lymph node bed may improve locoregional control. However, newer studies confirm that patients with biopsy-negative sentinel lymph nodes may not benefit from regional RT. Advanced MCC currently lacks a highly effective treatment as responses to chemotherapy are not durable. Recent work suggests that immunotherapy targeting the programmed cell death receptor 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint holds great promise in treating advanced MCC and may provide durable responses in a portion of patients. At the same time, high-throughput sequencing studies have demonstrated significant differences in the mutational profiles of tumors with and without the Merkel cell polyomavirus (MCV). An important secondary endpoint in the ongoing immunotherapy trials for MCC will be determining if there is a response difference between the virus-positive MCC tumors that typically lack a large mutational burden and the virus-negative tumors that have a large number of somatic mutations and predicted tumor neoantigens. Interestingly, sequencing studies have failed to identify a highly recurrent activated driver pathway in the majority of MCC tumors. This may explain why targeted therapies can demonstrate exceptional responses in case reports but fail when treating all comers with MCC. Ultimately, a precision medicine approach may be more appropriate for treating MCC, where identified driver mutations are used to direct targeted therapies. At a minimum, stratifying patients in future clinical trials based on tumor viral status should be considered as virus-negative tumors are more likely to harbor activating driver mutations.

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“…Although mutation in c-kit and PDGFR are rare events in MCCs, successful MCC patients treated with imatinib have been reported [48–50]. However, a Phase II clinical trial concluded that most MCCs progressed during the one or two cycles of treatment [51].…”

Section: Staging and Treatmentmentioning

confidence: 99%

Merkel Cell Carcinoma: Epidemiology, Target, and Therapy

et al. 2014

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Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin with a rising incidence. MCC has metastatic potential regardless the size of the primary tumor and a 5-year disease associated mortality rate is 46 %. Surgery and radiation are the mainstays of management for primary MCC. There is no evidence-based effective chemotherapy for recurrent or metastatic diseases to date. In-depth mechanistic studies in MCC have uncovered important cellular events and the association with a polyomavirus, which has provided direct evidence for molecular targeted and immunotherapy. Further perspective studies and clinical trials are warranted to provide reliable evidence of possible pitfalls and effectiveness of molecular targeted immunotherapy alone or in combination with chemotherapy in MCC.

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Clinical remission of Merkel cell carcinoma after treatment with imatinib

Cited by 31 publications

References 3 publications

Correlation of Merkel cell polyomavirus positivity with PDGFRα mutations and survivin expression in Merkel cell carcinoma

Correlation of Merkel cell polyomavirus positivity with PDGFRα mutations and survivin expression in Merkel cell carcinoma

Merkel Cell Carcinoma Therapeutic Update

Merkel Cell Carcinoma: Epidemiology, Target, and Therapy

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